Identification of ferroptosis-related molecular subtypes and a methylation-related ferroptosis gene prognostic signature in cervical squamous cell carcinoma.

PURPOSE: We aimed to investigate the molecular characteristics of cervical squamous cell carcinoma (CESC) by analyzing ferroptosis-related gene (FRG) expression data to predict prognosis. METHODS: Gene expression and clinicopathological data of patients with CESC were collected from the Cancer Genome Atlas and the Genotype-Tissue Expression databases. Using Cox regression analysis, we identified 21 FRGs associated with prognosis. Cluster analysis categorized patients into subgroups based on these genes and compared their clinicopathological, biological, and immune infiltration features. FRG methylation levels were examined, and a risk model based on such FRG methylation levels was constructed using LASSO and Cox regression analyses. The model's predictive capacity was validated, and the relationships between the risk score and immune infiltration, tumor microenvironment, and drug sensitivity were explored. FRG methylation in CESC tissues was validated by immunohistochemistry. RESULTS: We identified 21 FRGs associated with CESC prognosis. Patients were stratified into two subtypes based on these genes, they showed differences in prognosis, immune cell types, and immune checkpoint expression. A three-gene risk score (including AQP3, MGST1, and TFRC) was generated, and the low-risk group showed better overall survival. The high-risk and low-risk groups differed in terms of immune infiltration, gene mutations, and drug sensitivity. Experimental validation confirmed the upregulation of AQP3 and TFRC, whereas MGST1 expression was not significantly altered in CESC tissues compared with that in normal cervical tissues. CONCLUSION: This study highlights the potential role of FRG methylation in predicting CESC prognosis and provides a personalized assessment of immune responses in patients with CESC.